P647: SAFETY AND EFFECTIVENESS OF VENETOCLAX MONOTHERAPY IN R/R CLL PATIENTS WITH OR WITHOUT RISK-ASSOCIATED GENETIC MARKERS – DATA FROM THE OBSERVATIONAL VERVE STUDY
Authors: I. Schwaner, H. Hebart, C. Losem, T. Wolff, K. Famulla, J. Huelsenbeck, B. Schmidt, T. Nösslinger, D. Rossi
Journal: HemaSphere (2022)

Background: In chronic lymphocytic leukemia (CLL), the association of genetic markers such as del(17p), TP53 and IGHV status with disease prognosis is well established. In clinical trials, treatment with Venetoclax (Ven) monotherapy has shown promising efficacy and good tolerability in all subgroups1,2. However, there is limited real-world data on Ven usage in specific genetic subgroups. Aims: The non-interventional observational study VeRVe aims to investigate safety and effectiveness of Ven for treatment of CLL in a real world setting in Germany, Austria, and Switzerland. Here, we present VeRVe data focusing on Ven monotherapy in CLL patients with or without the genetic risk factors TP53 mut and/or del(17p) as well as IGHV status. Methods: CLL patients included in this study required therapy and were eligible for Ven monotherapy treatment according to local label3. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of month 6 and quarterly afterwards up to a maximum of 2 years. Response assessment can be documented at end of ramp-up, after 3, 12 and 24 months. Results: On Nov 4th, 2021, 77 patients were enrolled in the VeRVe study and received at least one dose of Ven monotherapy, 29 of which were female. 40 of them had TP53 aberrations (TP53 mut and/or del(17p)) and 27 were IGHV unmutated. For 14 patients TP53 mut status, for 10 patients del(17p) and for 40 patients IGHV status was not documented. At start of therapy, the median age of patients with TP53 aberrations was 73 years and 71 years for patients with wildtype (wt) TP53. In the population with TP53 aberrations, 40% had received 1, 28% 2 and 32% 3 or more prior therapies. In the population with wild-type (wt) TP53, 12% had received 1, 40% 2 and 48% 3 or more prior therapies. 80% of patients with TP53 aberration and 72% of patients with wt TP53 had at least 1 comorbidity. After 12 months of therapy, the best ORR (CR/CRi) was 74% (34%) in the total population. Thereby, the best ORR (CR/CRi) was 76% (43%) in patients with TP53 aberrations and 69% (27%) in patients without TP53 aberrations. When subdivided according to IGHV status, the best ORR (CR/CRi) was 83% (33%) in IGHV mutated and 85% (43%) in IGHV unmutated patients (see figure). Moreover, estimated PFS-rate after 1 year was at 80% in the total population. Thereby, estimated PFS-rate was at 78% in patients with TP53 aberrations and at 83% in patients with wt TP53. Estimated OS-rate after 1 year was 82% in the total population, 77% in patients with TP53 aberration and 84% in patients with wt TP53. With a median observation time of 294 days (range 0-1130), CTCAE grade AEs ≥3 were reported in 56%(n=43) of the total population, 53% (n=21) in the TP53 aberrant and 64% (n=16) in the TP53 wt population. SAEs were reported in 37% (n=39) of the total population, 45% (n=18) in the TP53 aberrant and 32% (n=8) in the TP53 wt population. Overall, 5 patients had a TLS with 3 of them being clinical TLS. No new safety signals were detected. Image:Summary/Conclusion: In summary, patients with TP53 aberration were slightly more pre-treated and suffered from co-morbidities more frequently than patients with wt TP53. Nevertheless, best ORR, estimated PFS-rates and OS-rates were comparably high in both populations. IGHV status was often not determined in this real-world study. For the available data, best ORR in IGHV mutated and IGHV unmutated patients were comparable. Surprisingly, CR/CRi rates were highest in patients with TP53 aberration or IGHV unmutated patients. Treatment was well tolerated in the overall population and all subgroups.